tbuckley/cabot-search huggingface dataset:
Gut Dysbiosis in Experimental Kidney Disease: A Meta-Analysis of Rodent Repository Data
Authors: David W. Randall, Julius Kieswich, Lesley Hoyles, Kieran McCafferty, Michael Curtis, Muhammed M. Yaqoob
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement Alterations in gut microbiota contribute to the pathophysiology of a diverse range of diseases, leading to suggestions that chronic uremia may cause intestinal dysbiosis that contributes to the pathophysiology of CKD. Various small, single-cohort rodent studies have supported this hypothesis. In this meta-analysis of publicly available repository data from studies of models of kidney disease in rodents, cohort variation far outweighed any effect of experimental kidney disease on the gut microbiota. No reproducible changes in animals with kidney disease were seen across all cohorts, although a few trends observed in most experiments may be attributable to kidney disease. The findings suggest that rodent studies do not provide evidence for the existence of “uremic dysbiosis” and that single-cohort studies are unsuitable for producing generalizable results in microbiome research. Background Rodent studies have popularized the notion that uremia may induce pathological changes in the gut microbiota that contribute to kidney disease progression. Although single-cohort rodent studies have yielded insights into host-microbiota relationships in various disease processes, their relevance is limited by cohort and other effects. We previously reported finding metabolomic evidence that batch-to-batch variations in the microbiome of experimental animals are significant confounders in an experimental study. Methods To attempt to identify common microbial signatures that transcend batch variability and that may be attributed to the effect of kidney disease, we downloaded all data describing the molecular characterization of the gut microbiota in rodents with and without experimental kidney disease from two online repositories comprising 127 rodents across ten experimental cohorts. We reanalyzed these data using the DADA2 and Phyloseq packages in R, a statistical computing and graphics system, and analyzed data both in a combined dataset of all samples and at the level of individual experimental cohorts. Results Cohort effects accounted for 69% of total sample variance ( P &lt;0.001), substantially outweighing the effect of kidney disease (1.9% of variance, P =0.026). We found no universal trends in microbial population dynamics in animals with kidney disease, but observed some differences (increased alpha diversity, a measure of within-sample bacterial diversity; relative decreases in Lachnospiraceae and Lactobacillus ; and increases in some Clostridia and opportunistic taxa) in many cohorts that might represent effects of kidney disease on the gut microbiota . Conclusions These findings suggest that current evidence that kidney disease causes reproducible patterns of dysbiosis is inadequate. We advocate meta-analysis of repository data as a way of identifying broad themes that transcend experimental variation.
Prevalence of Self-Reported Kidney Disease in Older Adults by Sexual Orientation: Behavioral Risk Factor Surveillance System Analysis (2014–2019)
Authors: Meghana Chandra, Mollie Hertel, Sean Cahill, Kevin Sakaguchi, Saumya Khanna, Shimontini Mitra, Jordi Luke, Meagan Khau, Jack Mirabella, Avareena Cropper
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement Studies discusses CKD disparities by age, race and ethnicity, and socioeconomics. However, despite well-documented disparities in CKD risk factors in LGBT+ adults, limited literature addresses CKD prevalence in this population. This analysis uses Behavioral Risk Factor Surveillance System (2014–2019) data to compare self-reported kidney disease prevalence in LGBT+ older adults (older than 50 years) with their heterosexual peers. Our findings indicate that LGBT+ older adults have higher rates of self-reported kidney disease and a higher incidence of CKD risks including smoking, activity limitations, adverse health outcomes, and limited access to health care, housing, and employment. These results support increasing access to screening for CKD risk factors, providing culturally responsive health care, and addressing societal drivers of vulnerability in older LGBT+ adults. Background Existing research documents disparities in CKD by age, race and ethnicity, and access to health care. However, research on CKD in lesbian, gay, bisexual, and trans (LGBT+) older adults, despite their higher rates of diabetes, heart disease, smoking, and alcohol use, is limited. Methods Pooled data from the Behavioral Risk Factor Surveillance System (2014–2019) for 22,114 LGBT+ adults and 748,963 heterosexuals aged 50 and older were used to estimate the prevalence of self-reported kidney disease. Logistic regressions were used to compare older adults by sexual orientation. Results Older LGBT+ men (adjusted odds ratio=1.3; 95% confidence interval [CI], 1.09–1.54) were more likely than their heterosexual counterparts to report kidney disease, after controlling for sociodemographic factors, health behaviors, access to health care, and self-reported coronary heart disease, HIV, and diabetes; LGBT+ men and women also reported higher incidences of known risk factors for CKD. For example, both LGBT+ men (odds ratio [OR]=1.39; [95% CI], 1.26–1.54) and LGBT+ women (OR=1.39; [95% CI], 1.25–1.55) were more likely to be smokers and have a higher incidence of activity limitations, adverse health outcomes, and limited access to health care, housing, and employment. Conclusion These results support increasing access to screenings for CKD risk factors, providing preventative education and culturally responsive and affirming care, and addressing other societal drivers of vulnerability in older LGBT+ adults. The findings also support the value of interventions that address the interaction between CKD risk factors and the social marginalization that older LGBT+ adults experience.
Protein Carbamylation and the Risk of ESKD in Patients with CKD
Authors: Sahir Kalim, Sophia Zhao, Mengyao Tang, Eugene P. Rhee, Andrew S. Allegretti, Sagar Nigwekar, S. Ananth Karumanchi, James P. Lash, Anders H. Berg
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement Protein carbamylation, a nonenzymatic post-translational protein modification partially driven by elevated blood urea levels, associates with mortality and adverse outcomes in patients with ESKD on dialysis. However, little is known about carbamylation's relationship to clinical outcomes in the much larger population of patients with earlier stages of CKD. In this prospective observational cohort study of 3111 individuals with CKD stages 2–4, higher levels of carbamylated albumin (a marker of protein carbamylation burden) were associated with a greater risk of developing ESKD and other significant adverse clinical outcomes. These findings indicate that protein carbamylation is an independent risk factor for CKD progression. They suggest that further study of therapeutic interventions to prevent or reduce carbamylation is warranted. Background Protein carbamylation, a post-translational protein modification partially driven by elevated blood urea levels, associates with adverse outcomes in ESKD. However, little is known about protein carbamylation's relationship to clinical outcomes in the much larger population of patients with earlier stages of CKD. Methods To test associations between protein carbamylation and the primary outcome of progression to ESKD, we measured baseline serum carbamylated albumin (C-Alb) in 3111 patients with CKD stages 2–4 enrolled in the prospective observational Chronic Renal Insufficiency Cohort study. Results The mean age of study participants was 59 years (SD 10.8); 1358 (43.7%) were female, and 1334 (42.9%) were White. The mean eGFR at the time of C-Alb assessment was 41.8 (16.4) ml/minute per 1.73 m 2 , and the median C-Alb value was 7.8 mmol/mol (interquartile range, 5.8–10.7). During an average of 7.9 (4.1) years of follow-up, 981 (31.5%) individuals developed ESKD. In multivariable adjusted Cox models, higher C-Alb (continuous or quartiles) independently associated with an increased risk of ESKD. For example, compared with quartile 1 (C-Alb ≤5.80 mmol/mol), those in quartile 4 (C-Alb &gt;10.71 mmol/mol) had a greater risk for ESKD (adjusted hazard ratio, 2.29; 95% confidence interval, 1.75 to 2.99), and the ESKD incidence rate per 1000 patient-years increased from 15.7 to 88.5 from quartile 1 to quartile 4. The results remained significant across numerous subgroup analyses, when treating death as a competing event, and using different assessments of eGFR. Conclusions Having a higher level of protein carbamylation as measured by circulating C-Alb is an independent risk factor for ESKD in individuals with CKD stages 2–4. Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_04_24_JASN0000000000000078.mp3
Stage IV lung cancer: the relevance of tumour profile for the construction of prognostic groups
Authors: Ramón Rami-Porta, Kwun M. Fong
Journal: European Respiratory Journal (2023)

Believe it or not, the first edition of the tumour, node and metastasis (TNM) classification, published by the Union for International Cancer Control (UICC) in 1968, did not have stages. Stages, that is the grouping of tumours classified by the TNM system that have similar prognosis, were introduced in the second edition, published in 1975. There were only three, with metastatic disease included in stage III. It was not until the third edition of 1978 that stage IV was created to accommodate metastatic spread. The three categories then established (MX, metastasis cannot be assessed; M0, no distant metastasis; and M1, distant metastasis) remained unchanged until the seventh edition of the TNM classification [1]. The UICC and the American Joint Committee on Cancer, the two institutions responsible for the promulgation and periodic revisions of the classification, decided then to eliminate the MX category based on the fact that the presence or absence of distant metastases could be assessed by a well-taken medical history and a thoroughly performed physical examination. The other innovations derived from the analyses of international databases undertaken by the International Association for the Study of Lung Cancer (IASLC), who had taken the responsibility to revise the forthcoming editions of the TNM classification of thoracic malignancies based on data collected internationally. To inform the seventh edition, the IASLC database included 81 495 evaluable patients diagnosed of small and non-small cell lung cancer (NSCLC) [2]. The combination of anatomic and non-anatomic prognostic factors will increase our capacity to prognosticate for an individual patient with stage IV lung cancer <http://bit.ly/3EssoFy>
The European Board of Accreditation in Pneumology (EBAP): reflections on 20 years promoting excellence in continuing medical education (CME) in respiratory medicine
Authors: Georgia Hardavella, Mona Lichtblau, Alf Henrik Andreassen, Jamil Jubrail, Edin Jusufovic, Ortrud Karg, Laurent Nicod, Angelo Petroianni, Paolo Palange
Journal: European Respiratory Journal (2023)

<b>EBAP holds a central overarching position across Europe and overseas as an independent accreditor of training centres and educational activities with transferable and recognised CME/CPD points across countries</b>https://bit.ly/3uZb5WT
Now we know: chronic exposure to air pollutants is a risk factor for the development of idiopathic pulmonary fibrosis
Authors: Lucile Sesé, Sergio Harari
Journal: European Respiratory Journal (2023)

<b>New evidence from the UK Biobank for the role of long-term exposure to NO<sub>2</sub>, NO<sub>x</sub> and fine particulate matter (PM<sub>2.5</sub>), and their interaction with genetic susceptibility in the development of idiopathic pulmonary fibrosis</b>http://bit.ly/3V3iJdM
Cell-free fetal DNA for genetic evaluation in Copenhagen Pregnancy Loss Study (COPL): a prospective cohort study
Authors: Tanja Schlaikjær Hartwig, Louise Ambye, Jennifer R Gruhn, Jesper Friis Petersen, Tine Wrønding, Letizia Amato, Andrew Chi-Ho Chan, Boyang Ji, Maiken Hemme Bro-Jørgensen, Lene Werge, Mette Marie Babiel Schmidt Petersen, Clara Brinkmann, Julie Boesgaard Ribberholt, Morten Dunø, Iben Bache, Markus J Herrgård, Finn Stener Jørgensen, Eva R Hoffmann, Henriette Svarre Nielsen, Henriette Svarre Nielsen, Tanja Schlaikjær Hartwig, Nina la Cour Freiesleben, Finn Stener Jørgensen Jørgensen, Louise Ambye, Sofie Bliddal, Therese Juhlin Søndergaard, Sisse Rye Ostrowski, Erik Sørensen, Margit Anita Hørup Larsen, Markus J. Herregård, Eva Hoffmann, Jenny Gruhn, Andy Chi Ho Chan, Astrid Marie Kolte, David Westergaard, Unnur þorsteinsdóttir, Kári Stefánsson, Hákon Jónsson, Ólafur þ. Magnússon, Valgerdur Steinthorsdottir, Lone Schmidt, Karsten Kristiansen, Pia Rørbæk Kamstrup, Mette Nyegaard, Maria Christine Krog, Ellen Christine Leth Løkkegaard, Helle Ejdrup Bredkjær, Charlotte Wilken-Jensen
Journal: The Lancet (2023)
Nintedanib in chILD: a small step, yes… but at least a step forward in a marathon!
Authors: David Gozal, Martin Kolb
Journal: European Respiratory Journal (2023)

<b>Interstitial lung disease in children lacks therapeutic options: as reported by a first RCT of its kind, a subset of these children presenting with a fibrotic phenotype may benefit from a therapeutic trial with nintedanib</b>https://bit.ly/3fuTYaW
Abstract 11318: Effect of Cardiac Resynchronization Therapy on Defibrillation Threshold Estimates
Authors: Amir Hedayati, Jamshid Alaeddini, John Payne, Steven Bailin, Sonar Pradhan, Ashish Oza, Michael Gold
Journal: Circulation (2010)

Introduction:  Defibrillation thresholds (DFTs) are typically stable over time among patients (pts) with implantable cardioverter defibrillators (ICD). However, the impact of cardiac resynchronization therapy (CRT) on DFTs has not been well studied. Accordingly, the present trial was a prospective evaluation of the effect of CRT and reverse remodeling on DFTs.   Methods:  This prospective, multicenter study evaluated 55 CRT-D pts. Echocardiography and DFTs were performed both at implant and 6-months post implant. All pts were implanted with a dual coil lead and DFTs were measured using a binary search method and tuned waveforms where the shock pulse width determined by shock impedance. Echocardiograms were analyzed by an independent core lab with a responder defined as a decrease of left ventricular end systolic volume (LVESV) > 15%.   Results:  The study cohort was 65% male with a mean age of 69.1 ± 14.4 years. The baseline EF was 27.6 ± 7.8% and NYHA class per specific activity scale was 2.9 ± 0.4. There was no significant change in DFT peak voltage, delivered energy (Joules) or shock impedace over time (Table 1). Similarly, reverse remodeling did not impact DFT at 6 months. In CRT responders (n = 32) the mean DFT was 415.6 ± 108.1 V at implant vs. 415.6 ± 124.7 V at 6-month (p = 0.9) and in non-responders (n = 19) the mean DFT was 452.6 ± 102 V at implant vs. 447.4 ± 112.4 V at 6-month (p = 0.8).   Conclusions:  DFTs were stable at 6 months in CRT patients with or without reverse remodeling.
Testing guidelines during times of crisis: challenges and limitations of developing rapid and living guidelines
Authors: Ibrahim K. El Mikati, Rebecca L. Morgan, M. Hassan Murad, Shahnaz Sultan, Yngve Falck-Ytter, Reem A. Mustafa
Journal: Clinical Microbiology and Infection (2023)

The start of the COVID-19 pandemic presented a situation in which there was an urgent need for decision-making that relates to diagnosis, but the evidence was lacking, of low certainty or constantly changing. Rapid and living guideline development methods were needed and had to be applied to rigorous guideline approaches, such as the Grading of Recommendations Assessment, Development, and Evaluation approach.To describe the process of developing rapid diagnosis guidelines when there is limited and imperfect available data at the time of crisis.Case example from four Infectious Disease Society of America COVID-19 diagnostic guidelines.As the world was experiencing panic with COVID-19, there were serious doubts about the feasibility of following a rigorous process for guideline development when timeliness was of extreme value. The Infectious Disease Society of America guideline panels supported by several methodologists strongly believed that at times of crisis, it is more important than ever to follow a rigorous process. The panel adopted a rapid and living systematic review methodology and applied the Grading of Recommendations Assessment, Development and Evaluation approach to four diagnosis guidelines despite the challenges of scarce and dynamic evidence. We describe the methodological details of the rapid and living approach (data extraction, meta-analysis, Evidence to Decision framework, and recommendation development), the challenge of resources, the challenge of scarce evidence, the challenge of rapidly changing evidence, as well as 'wins' from the Infectious Disease Society of America experience.Mitigation of pandemics relies on rapid and accurate diagnosis, which is challenged by many knowledge gaps. This necessitates emerging evidence is rapidly incorporated in a living fashion with several decisional and contextual factors to ensure the best public health strategies and care for patients. This process must be systematic and transparent for developing trustworthy guidelines and should be supported by all stakeholders, including researchers, editors, publishers, professional societies, and policymakers.
Correction:<i>Cardiopulmonary capacity and muscle strength in transgender women on long-term gender-affirming hormone therapy: a cross-sectional study</i>
Journal: British Journal of Sports Medicine (2023)

Methods:First sentence: "A cross-sectional study was carried out with 15 TW (34.2±5.2 years old), 15 cisgender men (CM) and 14 cisgender women (CW)."Correct: "A cross-sectional study was carried out with 15 non-athlete TW (34.2±5.2 years old), 14 cisgender men (CM) and 13 cisgender women (CW)."
Exercise as medicine for depressive symptoms? A systematic review and meta-analysis with meta-regression
Authors: Andreas Heissel, Darlene Heinen, Luisa Leonie Brokmeier, Nora Skarabis, Maria Kangas, Davy Vancampfort, Brendon Stubbs, Joseph Firth, Philip B Ward, Simon Rosenbaum, Mats Hallgren, Felipe Schuch
Journal: British Journal of Sports Medicine (2023)

Objective To estimate the efficacy of exercise on depressive symptoms compared with non-active control groups and to determine the moderating effects of exercise on depression and the presence of publication bias. Design Systematic review and meta-analysis with meta-regression. Data sources The Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, Embase, SPORTDiscus, PsycINFO, Scopus and Web of Science were searched without language restrictions from inception to 13 September2022 (PROSPERO registration no CRD42020210651). Eligibility criteria for selecting studies Randomised controlled trials including participants aged 18 years or older with a diagnosis of major depressive disorder or those with depressive symptoms determined by validated screening measures scoring above the threshold value, investigating the effects of an exercise intervention (aerobic and/or resistance exercise) compared with a non-exercising control group. Results Forty-one studies, comprising 2264 participants post intervention were included in the meta-analysis demonstrating large effects (standardised mean difference (SMD)=−0.946, 95% CI −1.18 to −0.71) favouring exercise interventions which corresponds to the number needed to treat (NNT)=2 (95% CI 1.68 to 2.59). Large effects were found in studies with individuals with major depressive disorder (SMD=−0.998, 95% CI −1.39 to −0.61, k=20), supervised exercise interventions (SMD=−1.026, 95% CI −1.28 to −0.77, k=40) and moderate effects when analyses were restricted to low risk of bias studies (SMD=−0.666, 95% CI −0.99 to −0.34, k=12, NNT=2.8 (95% CI 1.94 to 5.22)). Conclusion Exercise is efficacious in treating depression and depressive symptoms and should be offered as an evidence-based treatment option focusing on supervised and group exercise with moderate intensity and aerobic exercise regimes. The small sample sizes of many trials and high heterogeneity in methods should be considered when interpreting the results.
Noncutaneous immune-related adverse events predict overall and progression-free survival in patients with cutaneous toxicities after immune checkpoint inhibitor therapy
Authors: Maria S. Asdourian, Ted V. Jacoby, Nishi Shah, Tracey Otto, Leah L. Thompson, Edward Christopher Dee, Kerry L. Reynolds, Yevgeniy R. Semenov, Steven T. Chen
Journal: Journal of the American Academy of Dermatology (2023)
Comparison of neutralization activity against Omicron BA.2/BA.5 in sera from HCWs receiving heterologous/homologous COVID-19 vaccines
Authors: Masayuki Amano, Yasuko Ichikawa, Yukari Uemura, Shota Matsumoto, Kenji Maeda, Shuzo Matsushita, Shinya Shimada, Hiroaki Mitsuya
Journal: Journal of Infection (2023)
Multimodal deep learning of fundus abnormalities and traditional risk factors for cardiovascular risk prediction
Authors: Yeong Chan Lee, Jiho Cha, Injeong Shim, Woong-Yang Park, Se Woong Kang, Dong Hui Lim, Hong-Hee Won
Journal: npj Digital Medicine (2023)

Cardiovascular disease (CVD), the leading cause of death globally, is associated with complicated underlying risk factors. We develop an artificial intelligence model to identify CVD using multimodal data, including clinical risk factors and fundus photographs from the Samsung Medical Center (SMC) for development and internal validation and from the UK Biobank for external validation. The multimodal model achieves an area under the receiver operating characteristic curve (AUROC) of 0.781 (95% confidence interval [CI] 0.766-0.798) in the SMC and 0.872 (95% CI 0.857-0.886) in the UK Biobank. We further observe a significant association between the incidence of CVD and the predicted risk from at-risk patients in the UK Biobank (hazard ratio [HR] 6.28, 95% CI 4.72-8.34). We visualize the importance of individual features in photography and traditional risk factors. The results highlight that non-invasive fundus photography can be a possible predictive marker for CVD.
Common mouse models of tauopathy reflect early but not late human disease
Authors: Kathrin Wenger, Arthur Viode, Christoph N. Schlaffner, Patrick van Zalm, Long Cheng, Tammy Dellovade, Xavier Langlois, Anthony Bannon, Rui Chang, Theresa R. Connors, Derek Oakley, Bernhard Renard, Juri Rappsilber, Bradley Hyman, Hanno Steen, Judith A. Steen
Journal: Molecular Neurodegeneration (2023)

Mouse models that overexpress human mutant Tau (P301S and P301L) are commonly used in preclinical studies of Alzheimer's Disease (AD) and while several drugs showed therapeutic effects in these mice, they were ineffective in humans. This leads to the question to which extent the murine models reflect human Tau pathology on the molecular level.